Inhibition of airway remodeling in IL-5-deficient mice.
Inhibition of airway remodeling in IL-5-deficient mice.
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DOI：
10.1172/jci19133
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发表时间：
2004-02
期刊：
影响因子：
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通讯作者：
J. Y. Cho;Marina Miller;Kwang Je Baek;J. Han;J. Nayar;S. Lee;K. Mcelwain;Shauna McElwain;
中科院分区：
文献类型：
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作者：
J. Y. Cho;Marina Miller;Kwang Je Baek;J. Han;J. Nayar;S. Lee;K. Mcelwain;Shauna McElwain;
为探讨IL-5在气道重塑中的作用，用OVA致敏IL-5基因缺陷小鼠和WT小鼠，重复给药3个月。与OVA攻击的WT小鼠相比，IL-5缺陷小鼠的支气管周围纤维化(总肺胶原含量、支气管周围胶原Ⅲ和V型胶原含量)和支气管周围平滑肌(支气管周围平滑肌层厚度、α-平滑肌肌动蛋白免疫染色)显著减少。WT小鼠的主要碱性蛋白和转化生长因子-β染色阳性的支气管周细胞数量显著增加。相比之下，IL-5缺乏的小鼠的主要碱性蛋白染色阳性的支气管周围细胞数量显著减少，与之平行的是转化生长因子-β染色阳性的细胞数量的类似减少，这表明嗜酸性粒细胞是重塑的气道中转化生长因子-β的重要来源。与IL-5缺陷小鼠相比，OVA攻击诱导WT小鼠呼吸道上皮细胞α-Vbeta6整合素表达水平显著升高，肺组织中生物活性转化生长因子-β水平显著升高。呼吸道上皮细胞α-Vbeta6整合素表达增加可能是潜在的转化生长因子-β活化增强的原因之一。这些结果提示IL-5、嗜酸性粒细胞、α-Vbeta6和转化生长因子-β在气道重塑中起重要作用。
To determine the role of IL-5 in airway remodeling, IL-5-deficient and WT mice were sensitized to OVA and challenged by repetitive administration of OVA for 3 months. IL-5-deficient mice had significantly less peribronchial fibrosis (total lung collagen content, peribronchial collagens III and V) and significantly less peribronchial smooth muscle (thickness of peribronchial smooth muscle layer, alpha-smooth muscle actin immunostaining) compared with WT mice challenged with OVA. WT mice had a significant increase in the number of peribronchial cells staining positive for major basic protein and TGF-beta. In contrast, IL-5-deficient mice had a significant reduction in the number of peribronchial cells staining positive for major basic protein, which was paralleled by a similar reduction in the number of cells staining positive for TGF-beta, suggesting that eosinophils are a significant source of TGF-beta in the remodeled airway. OVA challenge induced significantly higher levels of airway epithelial alphaVbeta6 integrin expression, as well as significantly higher levels of bioactive lung TGF-beta in WT compared with IL-5-deficient mice. Increased airway epithelial expression of alphaVbeta6 integrin may contribute to the increased activation of latent TGF-beta. These results suggest an important role for IL-5, eosinophils, alphaVbeta6, and TGF-beta in airway remodeling.